The adaptations for life on land have long puzzled biologists.
The question range from are feathers descendents of dinosaur scales, how did arms and legs evolve from fins, and from what ancient fish organ did the lung evolve?
Biologists have known that the co-development of the cardiovascular and pulmonary systems is a recent evolutionary adaption to life outside of water, coupling the function of the heart with the gas exchange function of the lung. And, the lung is one of the most recent organs to have evolved in mammals and is arguably the most vital for terrestrial life.
The coordinated maturation of the cells of these two systems is illustrated during embryonic development, when the primitive lung progenitor cells protrude into the primitive cardiac progenitor cells as the two organs develop in parallel to form the cardiopulmonary circulation.
A team from the Perelman School of Medicine, University of Pennsylvania, shows that the pulmonary vasculature, the blood vessels that connect the heart to the lung, develops even in the absence of the lung.
Mice in which lung development is inhibited still have pulmonary blood vessels, which revealed to the researchers that cardiac progenitors, or stem cells, are essential for cardiopulmonary co-development.
The Penn team, led by Edward E. Morrisey, PhD, professor of Medicine and Cell and Developmental Biology and scientific director of the Penn Institute for Regenerative Medicine, identified a population of multi-potent CardioPulmonary mesoderm Progenitor cells they named CPPs. The CPPs can be distinguished from many other early embryonic cells by the expression of a well-studied signaling molecule Wnt2.
Morrisey said that their data show that Wnt2-positive cells exist prior to lung development and help coordinate lung and heart co-development by generating cell types in both tissues.
The Morrisey lab began with a couple of simple questions: how do the lung and heart co-develop and what are the critical signals that regulate this process? The breakthrough in this work occurred when the team characterized the expression pattern of the Wnt2 gene.
Using cell lineage tracing analysis, they showed that Wnt2 cells generate single clones that, in turn, generate both heart and lung tissue, including cardiomyocytes and blood vessel cells like vascular smooth muscle.
Indeed, CPPs are capable of generating the vast majority of early embryonic cell types in the heart and lung. These studies also showed that the different cell lineages within the lung are related. For example, vascular smooth muscle and airway smooth muscle share a common progenitor cell in the lung.
The development of CPPs is regulated by the expression of another well-known protein called hedgehog, which is required for proper connection of the pulmonary vasculature to the heart. These studies show that hedgehog, which is also expressed by early lung progenitor cells, helps to promote CPPs to differentiate into the smooth muscle component of the pulmonary vasculature.
The study has been published in Nature.